PROJECT SUMMARY The pediatric clinical trials enterprise is too slow and expensive and too disconnected from the needs of children. Nearly 60% of drugs used in children and 90% used in newborns are prescribed off-label. These problems persist despite a strong regulatory framework for advancing evidence on innovative medical products. Transformation of the system requires collaboration among public and private stakeholders and innovative reengineering of the pediatric trials system, including methods to integrate/catalyze existing expertise, resources, and infrastructure. The Institute for Advanced Clinical Trials for Children (I-ACT), an independent 501(c)3 non-profit, was launched as the instantiation of the Advisory Report from Critical Path Institute?s Pediatric Trials Consortium. I-ACT?s mission/vision are fully aligned with the goals of RFA-FD-17-014 and focus on creating an integrated resource for pediatric product development, with sustainable global infrastructure to support all phases of pediatric clinical trials. To address the FDA?s call for a Global Pediatric Clinical Trials Network (GPCTN), our specific aims are: Aim 1 (Strategy & Planning): Provide a multi-stakeholder forum for addressing existing and future challenges and opportunities in advancing pediatric clinical trials of innovative medicines and devices. Aim 2 (Tools, Best Practices & Education): Develop, curate, and disseminate tools, knowledge, and best practices and produce educational materials and programs that advance pediatric clinical trials on innovative medicines and devices. Aim 3 (Infrastructure & Trials Execution): Create and continuously improve a sustainable global infrastructure dedicated to rapid and successful execution of pediatric clinical trials of innovative medicines and devices. These aims subsume the 13 core functions for the GPCTN in the Advisory Report. I-ACT will lead the Administrative and Strategic Core of the GPCTN, ensuring successful execution of all network activities. PEDSnet will be the Data and Learning Core. PEDSnet is composed of the nation?s leading children?s research hospitals and condition-specific networks and provides hundreds of clinical sites and a resource (5.3M children) for data-driven feasibility and observational studies. Critical Path Institute, will lead the Regulatory Science Core and projects in key populations (e.g. newborns, rare diseases) and drug development tools. The National Capital Consortium for Pediatric Device Innovation, funded by FDA, is one of the strongest and successful pediatric device research networks in the world, and will lead the Device Core. I-ACT includes numerous global stakeholders whose commitment and expertise are essential GPCTN resources. The GPCTN will have the capacity to meet the demands of 50% of pediatric trials of innovative medicines/devices. Our approach will ensure that pediatric plans/protocols are created and conducted to enable timelier pediatric labeling, with a focus on outcomes. Our approach creates change that is inclusive of stakeholder perspectives but not limited by tradition. We will improve the child health value of projects to get it right the first time, producing a transformed and integrated global pediatric clinical trials infrastructure.